The combined use of a plurality of different anesthetics is common practice in modern anesthesia technique. The task of the anesthesiologist is to set the dosages of the individual anesthetics and thus to control the course of the anesthesia. The action of the combined anesthetics does not correspond, as a rule, to the sum of the individual actions, but there are interactions. This makes the setting of the dosages of the individual anesthetics a complicated task.
Based on the concentrations of the active ingredients at the site of the action, it is now possible to estimate an action on the basis of common interaction models. The data on which the model is based are usually obtained experimentally in studies on patients and volunteers and analyzed by means of statistical methods to form a model (compare, e.g., Greco W. R. et al., Application of a new approach for the quantitation of drug synergism to the combination of cis-diaminoedichloroplatinum and 1-beta-D-arabinofuranosylcytosine, Cancer Res., 1990, Sep. 1; 50(17) :5318-27 Minto C. F. et al., Response surface model for anesthetic drug interactions. Anesthesiology, 2000, June 92(6), 1603-1616; Bouillon T. W. et al., Pharmacodynamic interaction between propofol and remifentanil regarding hypnosis, tolerance of laryngoscopy, bispectral index, and electroencephalographic approximate entrophy, Anesthesiology, June 2004; 100 (6): 1353-1372).
A certain value is obtained for each pair of concentration values from the interaction of two anesthetics for a certain anesthesia action parameter, e.g., for the probability that laryngoscopy will be tolerated. If the concentrations of two anesthetics are plotted on the X and Y axes, an action or response surface will then be obtained, as it is shown, e.g., in FIG. 2 for the probability of the tolerance of laryngoscopy (TOL), left-hand figure, and the tolerance to shaking and shouting (TOSS), right-hand figure. A horizontal section through the response surface yields a curve, on which the particular anesthesia action parameter has the same value. These lines of equal action are called isoboles.
The concentrations of the anesthetics at the site of action or in the plasma can be calculated from the quantities of the anesthetics fed by means of so-called pharmacokinetic compartment models. The concentrations for intravenous anesthetics are calculated, for example, with two- to three-compartment models. Such a pharmacokinetic compartment model is schematically shown in FIG. 1. These models always comprise a central compartment, which corresponds to the concentration in the plasma. An effect compartment is usually attached to the central compartment in order to model the transport to the site of action and the duration of action of the anesthetic, which is associated therewith. Five-compartment models, with which especially the concentration in the compartment rich in vessels—which includes the brain (site of action)—can be approximated, are used for gaseous anesthetics (compare, e.g., Carpenter R. I. et al., Pharmacokinetics of inhaled anesthetics in humans: measurements during and after the simultaneous administration of enflurane, halothane, isoflurane, methoxyflurane, and nitrous oxide, Anesth. Analg., June 1986; 65 (6): 575-582; Yasuda N. et al., Comparison of kinetics of sevoflurane and isoflurane in humans. Anesth. Analg., March 1991; 72 (3): 316-324; Yasuda N. et al., Kinetics of desflurane, isoflurane, and halothane in humans, Anesthesiology, March 1991; 74 (3): 489-498).
The most advanced attempt at facilitating the handling of anesthesia devices during the administration of a plurality of drugs is described in the article “Development and evaluation of a graphical anesthesia drug display,” Noah D. Syroid et al., Anesthesiology, Vol. 96, No. 3, March 2002. It is proposed there that the concentration of the individual drugs be approximated, recorded and extrapolated into the future by means of pharmacokinetic compartment models. Furthermore, the individual concentration curves are always represented on a display means as a curve as a function of the time. In addition, bar graphs, in which the individual contributions of each drug are shown next to each other in the form of a differently colored bar, are provided for certain anesthesia action parameters. In addition, the contribution of synergistic interaction to the action parameter is plotted on a gray area.